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  1. Article: Nitrosative Stress in Astronaut Skeletal Muscle in Spaceflight.

    Blottner, Dieter / Moriggi, Manuela / Trautmann, Gabor / Furlan, Sandra / Block, Katharina / Gutsmann, Martina / Torretta, Enrica / Barbacini, Pietro / Capitanio, Daniele / Rittweger, Joern / Limper, Ulrich / Volpe, Pompeo / Gelfi, Cecilia / Salanova, Michele

    Antioxidants (Basel, Switzerland)

    2024  Volume 13, Issue 4

    Abstract: Long-duration mission (LDM) astronauts from the International Space Station (ISS) (>180 ISS days) revealed a close-to-normal sarcolemmal nitric oxide synthase type-1 (NOS1) immunoexpression in myofibers together with biochemical and quantitative qPCR ... ...

    Abstract Long-duration mission (LDM) astronauts from the International Space Station (ISS) (>180 ISS days) revealed a close-to-normal sarcolemmal nitric oxide synthase type-1 (NOS1) immunoexpression in myofibers together with biochemical and quantitative qPCR changes in deep calf soleus muscle. Nitro-DIGE analyses identified functional proteins (structural, metabolic, mitochondrial) that were over-nitrosylated post- vs. preflight. In a short-duration mission (SDM) astronaut (9 ISS days), s-nitrosylation of a nodal protein of the glycolytic flux, specific proteins in tricarboxylic acid (TCA) cycle, respiratory chain, and over-nitrosylation of creatine kinase M-types as signs of impaired ATP production and muscle contraction proteins were seen. S-nitrosylation of serotransferrin (TF) or carbonic anhydrase 3 (CA3b and 3c) represented signs of acute response microgravity muscle maladaptation. LDM nitrosoprofiles reflected recovery of mitochondrial activity, contraction proteins, and iron transporter TF as signs of muscle adaptation to microgravity. Nitrosated antioxidant proteins, alcohol dehydrogenase 5/S-nitrosoglutathione reductase (ADH5/GSNOR), and selenoprotein thioredoxin reductase 1 (TXNRD1) levels indicated signs of altered redox homeostasis and reduced protection from nitrosative stress in spaceflight. This work presents a novel spaceflight-generated dataset on s-nitrosylated muscle protein signatures from astronauts that helps both to better understand the structural and molecular networks associated to muscular nitrosative stress and to design countermeasures to dysfunction and impaired performance control in human spaceflight missions.
    Language English
    Publishing date 2024-04-02
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2704216-9
    ISSN 2076-3921
    ISSN 2076-3921
    DOI 10.3390/antiox13040432
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Effects of Omega-3 and Antioxidant Cocktail Supplement on Prolonged Bed Rest: Results from Serum Proteome and Sphingolipids Analysis.

    Barbacini, Pietro / Blottner, Dieter / Capitanio, Daniele / Trautmann, Gabor / Block, Katharina / Torretta, Enrica / Moriggi, Manuela / Salanova, Michele / Gelfi, Cecilia

    Cells

    2022  Volume 11, Issue 13

    Abstract: Physical inactivity or prolonged bed rest (BR) induces muscle deconditioning in old and young subjects and can increase the cardiovascular disease risk (CVD) with dysregulation of the lipemic profile. Nutritional interventions, combining molecules such ... ...

    Abstract Physical inactivity or prolonged bed rest (BR) induces muscle deconditioning in old and young subjects and can increase the cardiovascular disease risk (CVD) with dysregulation of the lipemic profile. Nutritional interventions, combining molecules such as polyphenols, vitamins and essential fatty acids, can influence some metabolic features associated with physical inactivity and decrease the reactive oxidative and nitrosative stress (RONS). The aim of this study was to detect circulating molecules correlated with BR in serum of healthy male subjects enrolled in a 60-day BR protocol to evaluate a nutritional intervention with an antioxidant cocktail as a disuse countermeasure (Toulouse COCKTAIL study). The serum proteome, sphingolipidome and nitrosoproteome were analyzed adopting different mass spectrometry-based approaches. Results in placebo-treated BR subjects indicated a marked decrease of proteins associated with high-density lipoproteins (HDL) involved in lipemic homeostasis not found in the cocktail-treated BR group. Moreover, long-chain ceramides decreased while sphingomyelin increased in the BR cocktail-treated group. In placebo, the ratio of
    MeSH term(s) Antioxidants/pharmacology ; Bed Rest ; Dietary Supplements ; Fatty Acids, Omega-3/pharmacology ; Humans ; Male ; Proteome ; Sphingolipids
    Chemical Substances Antioxidants ; Fatty Acids, Omega-3 ; Proteome ; Sphingolipids
    Language English
    Publishing date 2022-07-05
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells11132120
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Space Omics and Tissue Response in Astronaut Skeletal Muscle after Short and Long Duration Missions.

    Blottner, Dieter / Moriggi, Manuela / Trautmann, Gabor / Hastermann, Maria / Capitanio, Daniele / Torretta, Enrica / Block, Katharina / Rittweger, Joern / Limper, Ulrich / Gelfi, Cecilia / Salanova, Michele

    International journal of molecular sciences

    2023  Volume 24, Issue 4

    Abstract: The molecular mechanisms of skeletal muscle adaptation to spaceflight are as yet not fully investigated and well understood. The MUSCLE BIOPSY study analyzed pre and postflight deep calf muscle biopsies (m. soleus) obtained from five male International ... ...

    Abstract The molecular mechanisms of skeletal muscle adaptation to spaceflight are as yet not fully investigated and well understood. The MUSCLE BIOPSY study analyzed pre and postflight deep calf muscle biopsies (m. soleus) obtained from five male International Space Station (ISS) astronauts. Moderate rates of myofiber atrophy were found in long-duration mission (LDM) astronauts (~180 days in space) performing routine inflight exercise as countermeasure (CM) compared to a short-duration mission (SDM) astronaut (11 days in space, little or no inflight CM) for reference control. Conventional H&E scout histology showed enlarged intramuscular connective tissue gaps between myofiber groups in LDM post vs. preflight. Immunoexpression signals of extracellular matrix (ECM) molecules, collagen 4 and 6, COL4 and 6, and perlecan were reduced while matrix-metalloproteinase, MMP2, biomarker remained unchanged in LDM post vs. preflight suggesting connective tissue remodeling. Large scale proteomics (space omics) identified two canonical protein pathways associated to muscle weakness (necroptosis, GP6 signaling/COL6) in SDM and four key pathways (Fatty acid β-oxidation, integrin-linked kinase ILK, Rho A GTPase RHO, dilated cardiomyopathy signaling) explicitly in LDM. The levels of structural ECM organization proteins COL6A1/A3, fibrillin 1, FBN1, and lumican, LUM, increased in postflight SDM vs. LDM. Proteins from tricarboxylic acid, TCA cycle, mitochondrial respiratory chain, and lipid metabolism mostly recovered in LDM vs. SDM. High levels of calcium signaling proteins, ryanodine receptor 1, RyR1, calsequestrin 1/2, CASQ1/2, annexin A2, ANXA2, and sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA1) pump, ATP2A, were signatures of SDM, and decreased levels of oxidative stress peroxiredoxin 1, PRDX1, thioredoxin-dependent peroxide reductase, PRDX3, or superoxide dismutase [Mn] 2, SOD2, signatures of LDM postflight. Results help to better understand the spatiotemporal molecular adaptation of skeletal muscle and provide a large scale database of skeletal muscle from human spaceflight for the better design of effective CM protocols in future human deep space exploration.
    MeSH term(s) Humans ; Male ; Astronauts ; Muscle, Skeletal/metabolism ; Muscle, Skeletal/pathology ; Space Flight ; Time Factors ; Muscular Atrophy/etiology ; Muscular Atrophy/metabolism ; Muscular Atrophy/pathology ; Biopsy
    Language English
    Publishing date 2023-02-17
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms24044095
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Opposite Regulation of Homer Signal at the NMJ Postsynaptic Micro Domain between Slow- and Fast-Twitch Muscles in an Experimentally Induced Autoimmune Myasthenia Gravis (EAMG) Mouse Model.

    Schubert, Martin / Pelz, Andreas / Trautmann, Gabor / Block, Katharina / Furlan, Sandra / Gutsmann, Martina / Kohler, Siegfried / Volpe, Pompeo / Blottner, Dieter / Meisel, Andreas / Salanova, Michele

    International journal of molecular sciences

    2022  Volume 23, Issue 23

    Abstract: Accelerated postsynaptic remodelling and disturbance of neuromuscular transmission are common features of autoimmune neurodegenerative diseases. Homer protein isoform expression, crosslinking activity and neuromuscular subcellular localisation are ... ...

    Abstract Accelerated postsynaptic remodelling and disturbance of neuromuscular transmission are common features of autoimmune neurodegenerative diseases. Homer protein isoform expression, crosslinking activity and neuromuscular subcellular localisation are studied in mouse hind limb muscles of an experimentally induced autoimmune model of Myasthenia Gravis (EAMG) and correlated to motor end plate integrity.
    Language English
    Publishing date 2022-11-30
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms232315052
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Nitrosative Redox Homeostasis and Antioxidant Response Defense in Disused Vastus lateralis Muscle in Long-Term Bedrest (Toulouse Cocktail Study)

    Blottner, Dieter / Capitanio, Daniele / Trautmann, Gabor / Furlan, Sandra / Gambara, Guido / Moriggi, Manuela / Block, Katharina / Barbacini, Pietro / Torretta, Enrica / Py, Guillaume / Chopard, Angèle / Vida, Imre / Volpe, Pompeo / Gelfi, Cecilia / Salanova, Michele

    Antioxidants. 2021 Mar. 03, v. 10, no. 3

    2021  

    Abstract: Increased oxidative stress by reactive oxygen species (ROS) and reactive nitrogen species (RNS) is a major determinant of disuse-induced muscle atrophy. Muscle biopsies (thigh vastus lateralis, VL) obtained from healthy male subjects enrolled in the ... ...

    Abstract Increased oxidative stress by reactive oxygen species (ROS) and reactive nitrogen species (RNS) is a major determinant of disuse-induced muscle atrophy. Muscle biopsies (thigh vastus lateralis, VL) obtained from healthy male subjects enrolled in the Toulouse Cocktail bedrest (BR) study were used to assess efficacy of an antioxidant cocktail (polyphenols, omega-3, vitamin E, and selenium) to counteract the increased redox homeostasis and enhance the antioxidant defense response by using label-free LC–MS/MS and NITRO-DIGE (nitrosated proteins), qPCR, and laser confocal microscopy. Label-free LC–MS/MS indicated that treatment prevented the redox homeostasis dysregulation and promoted structural remodeling (TPM3, MYH7, MYBPC, MYH1, MYL1, HRC, and LUM), increment of RyR1, myogenesis (CSRP3), and skeletal muscle development (MUSTN1, LMNA, AHNAK). These changes were absent in the Placebo group. Glycolysis, tricarboxylic acid cycle (TCA), oxidative phosphorylation, fatty acid beta-oxidation, and mitochondrial transmembrane transport were normalized in treated subjects. Proteins involved in protein folding were also normalized, whereas protein entailed in ion homeostasis decreased. NITRO-DIGE analysis showed significant protein nitrosylation changes for CAT, CA3, SDHA, and VDAC2 in Treatment vs. Placebo. Similarly, the nuclear factor erythroid 2-related factor 2 (Nrf-2) antioxidant response element (Nrf-2 ARE) signaling pathway showed an enhanced response in the Treatment group. Increased nitrosative redox homeostasis and decreased antioxidant defense response were found in post-BR control (Placebo, n = 10) vs. the antioxidant cocktail treated group (Treatment, n = 10). Taken together, increased nitrosative redox homeostasis and muscle deterioration during BR-driven physical inactivity were prevented, whereas decreased antioxidant nitrosative stress defense response was attenuated by Treatment suggesting positive effects of the nutritional intervention protocol in bedrest.
    Keywords antioxidant activity ; beta oxidation ; confocal microscopy ; fatty acids ; glycolysis ; homeostasis ; males ; mitochondria ; muscle development ; muscles ; muscular atrophy ; nitrosylation ; nutritional intervention ; oxidative phosphorylation ; oxidative stress ; placebos ; polyphenols ; reactive nitrogen species ; reactive oxygen species ; selenium ; skeletal muscle ; tricarboxylic acid cycle ; vitamin E
    Language English
    Dates of publication 2021-0303
    Publishing place Multidisciplinary Digital Publishing Institute
    Document type Article
    ZDB-ID 2704216-9
    ISSN 2076-3921
    ISSN 2076-3921
    DOI 10.3390/antiox10030378
    Database NAL-Catalogue (AGRICOLA)

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  6. Article ; Online: Nerve-dependent distribution of subsynaptic type 1 inositol 1,4,5-trisphosphate receptor at the neuromuscular junction.

    Volpe, Pompeo / Bosutti, Alessandra / Nori, Alessandra / Filadi, Riccardo / Gherardi, Gaia / Trautmann, Gabor / Furlan, Sandra / Massaria, Gabriele / Sciancalepore, Marina / Megighian, Aram / Caccin, Paola / Bernareggi, Annalisa / Salanova, Michele / Sacchetto, Roberta / Sandonà, Dorianna / Pizzo, Paola / Lorenzon, Paola

    The Journal of general physiology

    2022  Volume 154, Issue 11

    Abstract: Inositol 1,4,5-trisphosphate receptors (IP3Rs) are enriched at postsynaptic membrane compartments of the neuromuscular junction (NMJ), surrounding the subsynaptic nuclei and close to nicotinic acetylcholine receptors (nAChRs) of the motor endplate. At ... ...

    Abstract Inositol 1,4,5-trisphosphate receptors (IP3Rs) are enriched at postsynaptic membrane compartments of the neuromuscular junction (NMJ), surrounding the subsynaptic nuclei and close to nicotinic acetylcholine receptors (nAChRs) of the motor endplate. At the endplate level, it has been proposed that nerve-dependent electrical activity might trigger IP3-associated, local Ca2+ signals not only involved in excitation-transcription (ET) coupling but also crucial to the development and stabilization of the NMJ itself. The present study was undertaken to examine whether denervation affects the subsynaptic IP3R distribution in skeletal muscles and which are the underlying mechanisms. Fluorescence microscopy, carried out on in vivo denervated muscles (following sciatectomy) and in vitro denervated skeletal muscle fibers from flexor digitorum brevis (FDB), indicates that denervation causes a reduction in the subsynaptic IP3R1-stained region, and such a decrease appears to be determined by the lack of muscle electrical activity, as judged by partial reversal upon field electrical stimulation of in vitro denervated skeletal muscle fibers.
    MeSH term(s) Calcium/metabolism ; Inositol ; Inositol 1,4,5-Trisphosphate Receptors ; Muscle, Skeletal/metabolism ; Neuromuscular Junction ; Receptors, Nicotinic
    Chemical Substances Inositol 1,4,5-Trisphosphate Receptors ; Receptors, Nicotinic ; Inositol (4L6452S749) ; Calcium (SY7Q814VUP)
    Language English
    Publishing date 2022-09-23
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 3118-5
    ISSN 1540-7748 ; 0022-1295
    ISSN (online) 1540-7748
    ISSN 0022-1295
    DOI 10.1085/jgp.202213128
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Preliminary Observations on Skeletal Muscle Adaptation and Plasticity in Homer 2

    Lorenzon, Paola / Furlan, Sandra / Ravara, Barbara / Bosutti, Alessandra / Massaria, Gabriele / Bernareggi, Annalisa / Sciancalepore, Marina / Trautmann, Gabor / Block, Katharina / Blottner, Dieter / Worley, Paul F / Zampieri, Sandra / Salanova, Michele / Volpe, Pompeo

    Metabolites

    2021  Volume 11, Issue 9

    Abstract: Homer represents a diversified family of scaffold and transduction proteins made up of several isoforms. Here, we present preliminary observations on skeletal muscle adaptation and plasticity in a transgenic model of Homer ... ...

    Abstract Homer represents a diversified family of scaffold and transduction proteins made up of several isoforms. Here, we present preliminary observations on skeletal muscle adaptation and plasticity in a transgenic model of Homer 2
    Language English
    Publishing date 2021-09-19
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2662251-8
    ISSN 2218-1989
    ISSN 2218-1989
    DOI 10.3390/metabo11090642
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Nitrosative Redox Homeostasis and Antioxidant Response Defense in Disused

    Blottner, Dieter / Capitanio, Daniele / Trautmann, Gabor / Furlan, Sandra / Gambara, Guido / Moriggi, Manuela / Block, Katharina / Barbacini, Pietro / Torretta, Enrica / Py, Guillaume / Chopard, Angèle / Vida, Imre / Volpe, Pompeo / Gelfi, Cecilia / Salanova, Michele

    Antioxidants (Basel, Switzerland)

    2021  Volume 10, Issue 3

    Abstract: Increased oxidative stress by reactive oxygen species (ROS) and reactive nitrogen species (RNS) is a major determinant of disuse-induced muscle atrophy. Muscle biopsies (thigh vastus lateralis, ...

    Abstract Increased oxidative stress by reactive oxygen species (ROS) and reactive nitrogen species (RNS) is a major determinant of disuse-induced muscle atrophy. Muscle biopsies (thigh vastus lateralis,
    Language English
    Publishing date 2021-03-03
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2704216-9
    ISSN 2076-3921
    ISSN 2076-3921
    DOI 10.3390/antiox10030378
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Reciprocal Homer1a and Homer2 Isoform Expression Is a Key Mechanism for Muscle

    Blottner, Dieter / Trautmann, Gabor / Furlan, Sandra / Gambara, Guido / Block, Katharina / Gutsmann, Martina / Sun, Lian-Wen / Worley, Paul F / Gorza, Luisa / Scano, Martina / Lorenzon, Paola / Vida, Imre / Volpe, Pompeo / Salanova, Michele

    International journal of molecular sciences

    2021  Volume 23, Issue 1

    Abstract: The molecular mechanisms of skeletal muscle atrophy under extended periods of either disuse or microgravity are not yet fully understood. The transition of Homer isoforms may play a key role during neuromuscular junction (NMJ) imbalance/plasticity in ... ...

    Abstract The molecular mechanisms of skeletal muscle atrophy under extended periods of either disuse or microgravity are not yet fully understood. The transition of Homer isoforms may play a key role during neuromuscular junction (NMJ) imbalance/plasticity in space. Here, we investigated the expression pattern of Homer short and long isoforms by gene array, qPCR, biochemistry, and laser confocal microscopy in skeletal muscles from male C57Bl/N6 mice (
    MeSH term(s) Animals ; Hindlimb Suspension/physiology ; Homer Scaffolding Proteins/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Muscle Proteins/metabolism ; Muscle, Skeletal/metabolism ; Muscular Atrophy/metabolism ; Neuromuscular Junction/metabolism ; Protein Isoforms/metabolism ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar ; Space Flight/methods ; Weightlessness
    Chemical Substances Homer Scaffolding Proteins ; Homer1 protein, mouse ; Homer2 protein, mouse ; Muscle Proteins ; Protein Isoforms
    Language English
    Publishing date 2021-12-22
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms23010075
    Database MEDical Literature Analysis and Retrieval System OnLINE

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